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Cited by 226Drug Transport and Resistance MechanismsLiver physiology and pathologyDrug-Induced Hepatotoxicity and Protection

The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.

Biliary excretion in primary rat hepatocytes cultured in a collagen-sandwich configuration

Liu, Xingrong, LeCluyse, Edward L., Brouwer, Kenneth R., Gan, Liang-Sheng L., Lemasters, John J., Stieger, Bruno, Meier, Peter J., Brouwer, Kim L. R.·1999·American Journal of Physiology-Gastrointestinal and Liver Physiology
DOI 10.1152/ajpgi.1999.277.1.g12
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Abstract

The objective of the present investigation was to examine the functional reestablishment of polarity in freshly isolated hepatocytes cultured between 2 layers of gelled collagen (sandwich configuration). Immunoblot analysis demonstrated that the canalicular multispecific organic anion transport protein (multidrug resistance-associated protein, Mrp2) was partially maintained in day 5 hepatocytes cultured in a sandwich configuration. Fluorescein-labeled taurocholate and carboxydichlorofluorescein were excreted into and concentrated in the bile canalicular lumen of day 5sandwich-cultured hepatocytes, resulting in formation of fluorescent networks in standard buffer (intact bile canaliculi). Confocal microscopy studies demonstrated that 1) carboxydichlorofluorescein that had concentrated in the canalicular lumen was released into the incubation buffer in the presence of Ca 2+ -free buffer (disrupted bile canaliculi), and 2) rhodamine-dextran, an extracellular space marker, was only able to diffuse into the canalicular lumen in the presence of Ca 2+ -free buffer. The cumulative uptake of [ 3 H]taurocholate in day 5 sandwich-cultured hepatocytes was significantly higher in standard buffer compared with Ca 2+ -free buffer, due to accumulation of taurocholate in canalicular spaces. When [ 3 H]taurocholate was preloaded in the day 5sandwich-cultured hepatocytes, taurocholate efflux was greater in Ca 2+ -free compared with standard buffer. The biliary excretion index of taurocholate, equivalent to the percentage of retained taurocholate in the canalicular networks, increased from ∼8% at day 0 to ∼60% at day 5 in sandwich-cultured hepatocytes. In summary, hepatocytes cultured in a collagen-sandwich configuration for up to 5 days establish intact canalicular networks, maintain Mrp2, reestablish polarized excretion of organic anions and bile acids, and represent a useful in vitro model system to investigate the hepatobiliary disposition of substrates.

Overview

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Crossref · 10.1152/ajpgi.1999.277.1.g12

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Citations

Cites

Research works printed but not linked: 5

  1. Adachi Y., 1991, Hepatology, 14, 655
  2. Groothuis G. M. M., 1996, J. Hepatol., 4, 3
  3. Liang D., 1993, Hepatology, 18, 1162
  4. Oude Elferink R. P. J., 1990, Am. J. Physiol., 258, G699
  5. Tarao K., 1982, Am. J. Physiol., 243, G253

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Metadata

Authors
Liu, X., LeCluyse, E. L., Brouwer, K. R., Gan, L.-S. L., Lemasters, J. J., Stieger, B., Meier, P. J., & Brouwer, K. L. R.
Affiliations
  • Division of Drug Delivery and Disposition, School of Pharmacy, and
  • Division of Bioanalysis and Drug Metabolism, Glaxo Wellcome, Inc., Research Triangle Park, North Carolina 27709; and
  • University of North Carolina at Chapel Hill (US)
  • University Hospital Zurich (CH)
ORCID
Venue
American Journal of Physiology-Gastrointestinal and Liver Physiology
Publisher
American Physiological Society
Published
1999-07-01
Volume
277
Issue
1
Pages
G12-G21
ISSN
  • 0193-1857 (ISSN-L)
  • 1522-1547
DOI
10.1152/ajpgi.1999.277.1.g12
OpenAlex
W2101528448
Semantic Scholar
501c1cfc2938afc5aa6a1bdf0351de034d80a0bc
Cited by
226
References
30
Citations by year
2026: 2 · 2025: 5 · 2024: 5 · 2023: 2 · 2022: 6 · 2021: 7 · 2020: 4 · 2019: 5 · 2018: 5 · 2017: 8 · 2016: 9 · 2015: 16 · 2014: 12 · 2013: 21 · 2012: 11
FWCI
1.56
Type
journal article
Language
en
Open access
closed
Locations
  • American Journal of Physiology-Gastrointestinal and Liver Physiology (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of General Medical Sciences (R01GM041935, GM 41935)
Topics
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
Keywords
biliary excretion, hepatocyte polarity, MRP2, taurocholate, bile canaliculi, organic anion transport, bile acid efflux
MeSH terms
Animals, Bile, Carrier Proteins, Cell Membrane, Cells, Cultured, Collagen, Cytological Techniques, Fluoresceins, Liver, Male, Taurocholic Acid, Time Factors, Immunoblotting, Cell Polarity, Rats, Wistar, Anion Transport Proteins, Rats

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